Presentation of HIV-1 Envelope Trimers on the Surface of Silica Nanoparticles

J Pharm Sci. 2020 Jan;109(1):911-921. doi: 10.1016/j.xphs.2019.10.059. Epub 2019 Nov 1.


Inducing immune responses protecting from HIV infection or at least controlling replication poses a huge challenge to modern vaccinology. An increasingly discussed strategy to elicit a potent and broad neutralizing antibody response is the immobilization of HIV's trimeric envelope (Env) surface receptor on a nanoparticulate carrier. As a conceptual proof, we attached an Env variant (BG505 SOSIP.664) to highly stable and biocompatible silica nanoparticles (SiNPs) via site-specific covalent conjugation or nonspecific adsorption to SiNPs. First, we demonstrated the feasibility of SiNPs as platform for Env presentation by a thorough characterization process during which Env density, attachment stability, and antigenicity were evaluated for both formulations. Binding affinities to selected antibodies were in the low nanomolar range for both formulations confirming that the structural integrity of Env is retained after attachment. Second, we explored the recognition of SiNP conjugates by antigen presenting cells. Here, the uptake of Env attached to SiNPs via a site-specific covalent conjugation was 4.5-fold enhanced, whereas adsorbed Env resulted only in a moderate 1.4-fold increase compared with Env in its soluble form. Thus, we propose SiNPs with site-specifically and covalently conjugated Env preferably in a high density as a promising candidate for further investigations as vaccine platform.

Keywords: HIV/AIDS; envelope; nanoparticle(s); protein delivery; silica; vaccine delivery.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / chemistry*
  • AIDS Vaccines / metabolism
  • AIDS Vaccines / pharmacology
  • Adsorption
  • Animals
  • Antibodies, Neutralizing / metabolism
  • Antibody Affinity
  • Binding Sites, Antibody
  • Cells, Cultured
  • Dendritic Cells / metabolism
  • Drug Carriers*
  • Drug Compounding
  • HIV Envelope Protein gp120 / chemistry*
  • HIV Envelope Protein gp120 / metabolism
  • HIV Envelope Protein gp120 / pharmacology
  • HIV Envelope Protein gp41 / chemistry*
  • HIV Envelope Protein gp41 / metabolism
  • HIV Envelope Protein gp41 / pharmacology
  • Male
  • Mice, Inbred C57BL
  • Nanoparticles*
  • Nanotechnology
  • Proof of Concept Study
  • Protein Multimerization
  • Protein Structure, Quaternary
  • Silicon Dioxide / chemistry*
  • Surface Properties


  • AIDS Vaccines
  • Antibodies, Neutralizing
  • Drug Carriers
  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp41
  • gp120 protein, Human immunodeficiency virus 1
  • gp41 protein, Human immunodeficiency virus 1
  • Silicon Dioxide